Fig. 1
Potential mechanisms of action for the anti-migraine effect of the Ca2+ channel blocker flunarizine. Flunarizine affects the production and release of nitric oxide in canine cerebral arteries by blocking the influx of Ca.2+ induced by action potentials at nerve terminals [3] and increases the threshold for cortical spreading depression [4, 5]. Moreover, flunarizine antagonizes the dopamine D2 receptor [6], and has antihistaminergic effects through targeting of the H1 receptor [7]. Calcium channel blockers can affect the serotonergic system [8, 9] and prolonged treatment with flunarizine results in decreased activity of 5-HT1 receptors in the hippocampus and cerebral cortex of rats [8]. The therapeutic dose of flunarizine for the treatment of migraine is unlikely to exert calcium antagonistic effects on cerebral vessels [1]